Generic patient self-report and investigator report instruments of therapeutic safety and tolerability.

A patient self-report instrument was designed as a patient event index that maps to a parallel investigator instrument. Event importance (a composite of severity, frequency, and duration) was reported, but attribution was not required. The patient instrument used a checklist but also allowed for spontaneous reporting for new or unusual events. The investigator instrument (also a checklist) includes all events reported by the patient, as well as events such as signs, investigations, and diagnoses that would not generally be known to the patient. Presently, both patient and investigator instruments are to be used alongside current methods of adverse event reporting in clinical trials. The patient instrument would serve as a safety/tolerability index, whereas the investigator instrument would be a fully quantifiable (appropriately weighted), standardized adverse event index. As in many methodological projects in medicine, the overriding problem was the tradeoff between validity (comprehensiveness and accuracy) and feasibility (clarity and short administration time) in instrument development. A summary of pilot studies and results of instrument reliability and validity are presented.

Standardized assessment of adverse events in rheumatology clinical trials: summary of the OMERACT 7 drug safety module update.

A presentation, demonstration, and discussion of recently developed adverse event instruments were the topics for the OMERACT 7 Drug Safety Module. The module began with a plenary introducing the needs and challenges of adverse event ascertainment. It was followed by a review of module work from previous OMERACT meetings on a prototype coding instrument (Rheumatology Common Toxicity Criteria), then a brief description of the process behind the recently developed patient self-report and investigator report adverse event instruments. These current instruments are designed for use in controlled trials although they could be used in other settings. The instruments rely primarily on patient self-reporting using a checklist, which the investigator then folds into a parallel structured but more medically sophisticated instrument. In pilot testing, this innovative dual-use system has shown reliability and acceptability, while preserving validity. A "stakeholder panel" of representatives from 8 sectors followed--patient, nurse investigator, regulator, clinician scientist, industry, OMERACT, global public health/WHO, and Cochrane Collaboration--for their perspectives on the needs, challenges, and potential ways forward for adverse event ascertainment and reporting in clinical trials. At the breakout session small focus groups participated in hands-on interactive testing of one of 3 versions of the instruments, which differ in degree of comprehensiveness. Each focus group had a participatory patient with rheumatoid arthritis. At a second plenary there was group feedback by rapporteurs and presentation of results from pilot studies of iterative testing of validity, reliability, and feasibility of the instruments. During plenary discussion a frequent suggestion for improvement was to refine the process so that event ascertainment could be done entirely using the patient instrument with minimal input from the investigator at the visit, if patient-investigator agreement was high. Most found the patient checklist attractive, particularly if the patient instrument was shown to be reliable and valid. Finally, a future research agenda was discussed.